DESCRIPTION: The tau protein is involved in organizing microtubules which form and maintain the neuronal axon. The neuronal tau transcript produces multiple isoforms of the protein. The splicing mechanisms modulating the C-terminal variants of tau and the role they play in neurons during development and neurodegeneration will be elucidated. The specific aims are to 1) isolate factors which inhibit the splicing of exon 10; 2) characterize trans factors involved in the alternative splicing of exon; and 3) study the expression and over-expression of the C- terminal variants during development.